Iterative Experimental-Computational Design of Hydrogel Systems for Biomedical Applications

生物医学应用水凝胶系统的迭代实验计算设计

• 批准号: 1463432
• 负责人: Ilinca Stanciulescu
• 金额: $ 45万
• 依托单位: William Marsh Rice University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-06-01 至 2019-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1463432&HistoricalAwards=false
• 关键词: Iterative; Experimental; Computational; Design; Hydrogel

This award supports fundamental research on methods for the design of engineered biomaterials. Historically, engineering of biomaterials has focused on biological effects but often ignored the advanced material fabrication and characterization needed to realize the desired biomechanical behavior. This research considers anisotropic and layered hydrogels for tissue engineering applications. The outcome of the research would be a methodology for the design these biomaterials. It integrates manufacturing and biomechanical characterization with the goal to arrive at biomaterials that correspond to complex tissues in the human body. Three target tissues are considered: trachea, intervertebral disks and heart valves. The research outcomes would greatly improve and accelerate the engineering process and thereby make engineered biomaterials more readily available. The outcomes of the research endeavor will also be integrated into educational initiatives through direct involvement of students in research, the development of new educational materials, and mentoring of undergraduate senior design teams.This project's approach is an iterative design methodology for anisotropic and layered hydrogel systems with regional dependent properties. It integrates manufacturing processes, experimental and computational characterization of the microstructured hydrogel systems to arrive at biomaterials that mimic connective tissues. Tissues with fibrous reinforcements (trachea), with layered structure (intervertebral disks), and tissue both patterned and layered (heart valves) are considered. The combined in silico-in vitro design process relies on fundamental advances at the interface between manufacturing, experimental and computational mechanics of soft materials, as well as mathematics. The iterative design starts with the preparation of samples of patterned or layered hydrogels, which will follow the topology of the specific tissue. Molecular weights for layers and for fiber patterns will be chosen such that the global stiffness approximates that of the real tissue in its most common state (e.g., compression for intervertebral disk). Photolithography and staged crosslinking will be used to manufacture materials. Samples will be tested in tension, compression, and bending. Computational models for the biomechanical response will be established which integrate the experimental data through constitutive formulations. Coarse level numerical optimization is performed in a reduced parameter space to approach the target behavior in all possible stress and deformation states encountered by the specific tissues. Further fabrication and experiments on hydrogel systems with more complex heterogeneity are then enabled based on the initial results. Hydrogel systems mimicking the tissue of interest would emerge from exercising the approach in the full parameter space such that optimal topologies and composition are achieved.

该奖项支持工程生物材料设计方法的基础研究。 从历史上看，生物材料工程一直专注于生物效应，但往往忽视了实现所需生物力学行为所需的先进材料制造和表征。本研究认为各向异性和分层水凝胶组织工程应用。研究的结果将是设计这些生物材料的方法。它集成了制造和生物力学表征，目标是获得与人体复杂组织相对应的生物材料。考虑三种靶组织：气管、椎间盘和心脏瓣膜。研究成果将大大改善和加速工程过程，从而使工程生物材料更容易获得。研究奋进也将通过学生直接参与研究、开发新教材和指导本科生高级设计团队等方式融入教育计划。该项目的方法是针对具有区域依赖性质的各向异性和分层水凝胶系统的迭代设计方法。它集成了微结构水凝胶系统的制造工艺、实验和计算表征，以获得模仿结缔组织的生物材料。 考虑具有纤维增强的组织（气管）、具有分层结构的组织（椎间盘）以及图案化和分层的组织（心脏瓣膜）。硅体外设计过程的结合依赖于软材料的制造，实验和计算力学以及数学之间的界面的基本进展。迭代设计从制备图案化或分层水凝胶样品开始，其将遵循特定组织的拓扑结构。将选择层和纤维图案的分子量，使得整体刚度近似于真实的组织在其最常见状态下的刚度（例如，椎间盘压迫）。 光刻和分阶段交联将用于制造材料。将对样品进行拉伸、压缩和弯曲试验。将建立生物力学响应的计算模型，该模型通过本构公式整合实验数据。 在简化的参数空间中进行粗级数值优化，以接近特定组织遇到的所有可能的应力和变形状态下的目标行为。然后，基于初步结果，能够对具有更复杂异质性的水凝胶系统进行进一步的制造和实验。 模仿感兴趣的组织的水凝胶系统将从在全参数空间中实施该方法中出现，使得实现最佳拓扑结构和组成。